Corticobasal degeneration with deep white matter lesion diagnosed by brain biopsy

Abstract

Corticobasal degeneration (CBD) is a rare progressive neurodegenerative disorder characterized by asymmetric presentation of cerebral cortex signs, cortical sensory disturbance and extrapyramidal signs. Herein, we report a case of a 66‐year‐old Japanese woman who presented with apraxia of the right hand. She subsequently developed postural instability and cognitive impairments that rapidly worsened. One and a half years later, the patient was wheelchair‐bound and severely demented. Brain magnetic resonance imaging revealed left dominant atrophy of the frontoparietal lobe. There was a hyperintense lesion in the deep white matter expanding toward the subcortical area on fluid‐attenuated inversion recovery (FLAIR) images. In order to rule out the possibility of an intracranial tumor such as an astrocytoma or malignant lymphoma, we performed a brain biopsy of the left frontal middle gyrus. The patient became bedridden and showed akinetic mutism 1 year after biopsy. Pathological examination revealed a large amount of 4‐repeat tau‐immunoreactive neuropil threads scattered predominantly in the corticomedullary junction and tau‐immunoreactive structures, consistent with CBD. Immunostaining for p53 showed no positive cells, and there were very few Ki‐67‐positive cells. On immunoblots of sarkosyl‐insoluble brain extracts, a major doublet of 64 and 68 kDa full‐length tau with two closely related fragments of approximately 37 kDa were detected. Based on these results, the patient was pathologically diagnosed as having CBD, excluding the possibility of tumor. Taken together with previous similar case reports, our findings indicate that a deep white matter hyperintense lesion on FLAIR images may be a useful clue to CBD, predicting rapid clinical progression with severe dementia based on severe white matter degeneration with a large amount of tau accumulation on pathological examination.

High-contrast in-vivo imaging of tau pathologies in Alzheimer’s and non-Alzheimer’s disease tauopathies

“…A clinical phenotype case of corticobasal syndrome (CBS) underwent a brain biopsy to investigate the presence of a tumor in consideration of a low-intensity lesion discovered by Tl-weighted MRI as reported by Arakawa et al . (Arakawa et al, 2020) (Figure S5). Neuropathological and biochemical examinations of the biopsied sample from the middle frontal gyrus revealed the presence of anti-four-repeat tau-specific antibody (RD4) and/or GB positive astrocytic plaques, ballooned neurons, neuropil threads, and coiled bodies resulting from the formation of insoluble four-repeat tau aggregates, which are characteristic of CBD (Arakawa et al, 2020) (Figure 6a).…”

“…(Arakawa et al, 2020) (Figure S5). Neuropathological and biochemical examinations of the biopsied sample from the middle frontal gyrus revealed the presence of anti-four-repeat tau-specific antibody (RD4) and/or GB positive astrocytic plaques, ballooned neurons, neuropil threads, and coiled bodies resulting from the formation of insoluble four-repeat tau aggregates, which are characteristic of CBD (Arakawa et al, 2020) (Figure 6a). Subsequent PET scans of this case showed negativity for 11 C-PiB and notable increases of 18 F-PM-PBB3 retentions in the primary motor cortex, basal ganglia, and brainstem consistent with the regional localization of CBD tau pathologies (Kouri et al, 2011), and middle frontal gyrus (Figure 6a and S5)…”

“…In addition, diagnoses of some patients were also validated according to their neuropathological examinations. One CBS patient was confirmed with CBD according to brain tissue biopsy before the PET scan (Arakawa et al, 2020); each of the PSP-Richardson and bvFTD patients was also neuropathologically diagnosed as PSP and PiD (Cairns et al, 2007) by autopsies after two years and one year after each PET scan, respectively.…”

High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer’s and Non-Alzheimer’s Disease Tauopathies

“…We obtained histopathological evidence that in-vivo 18 S5). Neuropathological and biochemical examinations of the biopsied sample from the middle frontal gyrus revealed the presence of anti-four-repeat tau-specific antibody (RD4) and/or GB positive astrocytic plaques, ballooned neurons, neuropil threads, and coiled bodies resulting from the formation of insoluble four-repeat tau aggregates, which are characteristic of CBD (Arakawa et al, 2020) (Figure 6a).…”

Neuroimaging Advances in Parkinson's Disease and Atypical Parkinsonian Syndromes

“…The predominant clinical syndrome in CBS (extrapyramidal vs. cognitive) was associated closely to the regional atrophy patterns ( 123 ). On fluid-attenuated inversion recovery images, subcortical WM hyperintensities with ventricular dilation (greater in the more affected lobe) were reported ( 157 ), however, these changes are not specific to CBS/CBD.…”